Therapeutic advances in pediatric neurooncology over the last two decades have been limited. New clinical research opportunities exist including novel approaches in the areas of cytotoxic drugs, radiation therapy and immunotherapy which require evaluation. No single institution accrues sufficient numbers of children with brain tumors to conduct trials of such new approaches in a timely fashion, and only a limited number of institutions have the sophisticated equipment and skills required to implement and evaluate such therapies. Therefore, to expeditiously evaluate innovative therapies, a Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) is required. The University of Washington Pediatric Neuro-Oncology Program brings the requisite personnel, resources and research expertise, discussed in this application, to contribute substantially to the goals of the PBTCTC. The Pediatric Neuro-Oncology Program was established in 1980 and was thus one of the initial programs recognizing the need for multidisciplinary care of children with brain tumors. The program includes a broad range of clinical and laboratory investigators. The goal of this application is to describe the efforts of this broad multidisciplinary group on issues relevant to improving the outcome of children with brain tumors in concert with PBTCC. In particular, our extensive experience with leadership in national cooperative clinical trials in pediatric brain tumor therapy, together with leading programs in radiation therapy, neuroimaging, neurosurgery, and neuropathology provides the critical mass and expertise required to effectively contribute to clinical evaluation of innovative brain tumor treatments. Our laboratory-based investigations of the molecular aspects of pediatric and adult brain tumors as well as a unique institutional program aimed at developing targeted therapy for malignancies also have the potential to contribute to the development of novel approaches to brain tumor therapy, in concert with the PBTCTC. Specifically we propose to: 1) effectively contribute to the clinical trials program of the PBTCTC; 2) provide laboratory-based analysis of molecular aspects of brain tumors required for the development of novel prognostic and therapeutic approaches; 3) develop novel methods of imaging brain tumors, including methods for rapid assessment of response to therapy; 4) develop novel targeted therapies for brain tumors.